Efficacy of tacrolimus combined with methotrezate in the treatment of patients with refractory rheumatoid arthritis / 中华风湿病学杂志

Objective To assess the efficacy and safety of tacrolimus (TAC) combined with methotrexate (MTX) for the treatment of refractory rheumatoid arthritis (RA),and to compare it with cyclophosphamide (CTX) added to MTX for the treatment of refractory RA.Methods Thirty-six cases of refractory RA patients were divided into the observation group and the control group.TAC+MTX were used in the observation group,and CTX+MTX were used in the control group.We used repeated measures to analyze the variance and Fisher exact probability method to analyze the efficacy at 8 weeks and 24 weeks.Results The effective rate of the observation group in 8 weeks,24 weeks were 77.8％(14 cases) and 100％(18 cases) respectively,while those of the control group were 11.1％ (2 cases) and 44.4％(8 cases),it showed that both TAC+MTX and CTX+MTX in the treatment of refractory RA were effective,but the efficacy of TAC+MTX was better than CTX+MTX,the difference of C reactive protein (CRP) and disease activity score (DAS)28 was statistically significant (P＜0.05),and it could significantly improve the clinical symptoms and laboratory indexes.Conclusion TAC+MTX is effective and safe in treating refractory RA,and is worth of spreading.

Expression of unfolded protein response gene glucose regulated protein 78 and X-box binding protein 1 in esophageal squamous cell carcinoma and their clinical significance / 肿瘤研究与临床

Objective To investigate the expression of unfolded protein response (UPR) gene glucose regulated protein 78(GRP78) and X-box binding protein 1(XBP1) in esophageal squamous cell carcinoma, its effect on activation of the endoplasmic reticulum stress (ERS) and its mechanism in the growth of esophageal squamous cell carcinoma. Methods The expressions of GRP78 and XBP1 were detected by immunohistochemistry in 30 samples of esophageal squamous cell carcinoma and 30 samples of normal esophageal squamous epithelium. The correlation between expressions of both proteins and prognosis was analyzed. Results GRP78 positive rate was 83.3 %(25/30) in esophageal carcinoma, while the proportion was 20.0 %(6/30) in normal esophageal (χ2=25.833, P<0.05). XBP1 positive rate was 70.0 % (21/30) in esophageal carcinoma, while the proportion was 26.7%(8/30) in normal esophageal(χ2=20.872, P<0.05). The positive rates of GRP78 and XBP1 in invasive muscular layer of esophageal squamous cell carcinoma were significantly higher than those in invasive mucous layer. Conclusion GRP78 and XBP1 are highly expressed in esophageal squamous cell carcinoma, which may involve the occurrence and development of the esophageal carcinoma.

Evaluation of the right ventricular systolic function in patients with systemic lupus erythematosus by speckle tracking imaging / 中华风湿病学杂志

Objective To evaluate the right ventricular (RV) systolic function in patients with systemic lupus erythematosus (SLE) by speckle tracking imaging (STI).Methods A total of 40 cases with SLE were divided into two groups,SLE (24 cases) and SLE complicated with pulmonary arterial hypertension (PAH) (16 cases).Meanwhile,35 healthy subjects were used as control group.Longitudinal peak systolic strain (PSS) of the basal,mid,apical segments of the free wall of right ventricular and interventricular septum and suben-docardial myocardium of the whole right ventricular were measured by STI respectively.Every parameter was compared.And the main factors affecting the strain of the whole right ventricule were analyzed.T test,one-way ANVOA,SNK-q,Spearman's correlation and Pearson's correlation analysis were used for statistical analysis.Results ① In SLE group,strains of the whole RV(GLS RV) [(-22±4)％] and all segments of RV wall[the basal segments of free wall (bas FW) (-27±8)％ were lower than that of the control group (-26±4)％,(-33±6)％,respectively (t=-4.815,P=0.000; t=-3.619,P=0.001)].Tricuspid valve orifice peak velocity E/A and right ventricular ejection fraction were significantly different between SLE group and control group (P＜0.05).② In terms of conventional parameters and the strain of all segments of RV wall,bas FW and GLS RV were different between the SLE group [(-30±7)％,(-23.7±3.5)％,respectively] and SLE with PAH group [(-22±6)％,(-18.4±2.3)％,respectively] (t=-3.581,P=0.001; t=-5.769,P=0.000).③ The RV anterior wall thickness of the moderate-severe subgroup was significantly higher than that of the mild group [(5.0±0.8) mm,(4.3±0.8) mm; t=-2.49,P=0.017].GLS RV[(-19±4)％,(-24±7)％;t=-3.016,P=0.015],bas FW [(-22±9)％,(-35±6)％; t=-3.125,P=0.03] and bas IVS [(-19±6)％,(-24±6)％; t=-2.272,P=0.029] were significantly lower than that of the mild group.Conclusion Right ventricular function is decreased in patients with SLE.STI can be used objectively to assess the right ventricular longitudinal systolic function.

Study on Foxp3 promoter region methylation of mononuclear cells in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective By detecting the expression levels of Foxp3 in CD4+CD25+ regulatory T cells of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA),and the Foxp3 gene promoter region methylation to explore its role in the pathogenesis of RA.Methods Twenty-five RA patients and 10 healthy controls were selected,and the PBMCs were extracted by density gradient centrifugation.Foxp3 expression levels of CD4+CD25+ regulatory T cells were detected by flow cytometry.The real-time fluorescence quantitative PCR assay was used to detect the Foxp3 mRNA expression in PBMCs; and bisulfate processing gene sequencing was used to determinethe differences in Foxp3 gene promoter sequence methylation level of PBMCs.The comparison between groups was analyzed using one-way ANOVA; two sets of qualitative data were compared using Fisher's exact test.Results The expression levels of Foxp3 mRNA in the CD4+CD25+regulatory T cells of active RA patients (2.31±0.25) was significantly lower than inactive RA group (3.68±0.26) and healthy controls (5.67±0.34),the difference was statistically significant (P＜0.05).The Foxp3 mRNA expression level in inactive RA group was lower than that of the healthy controls (P＜0.05).Foxp3 promoter region-67,-74 sites of methylation level in PBMCs of RA patients (46％) was significantly higher than that of the healthy controls (6％).Conclusion Reduction in the number of CD4+CD25+ regulatory T cells may be involved in the pathogenesis of RA and Foxp3 gene promoter methylation levels plays a key role in this process.

The expression of proline-rich tyrosine kinase and its role in systemic lupus erythematosus / 中华风湿病学杂志

Objective To explore the possible role of proline-rich tyrosine kinase (Pyk2) in the pathogenesis of systemic lupus erythematosus (SLE).Methods The expression of Pyk2 in the peripheral blood mononuclear cells (PBMCs) of 50 patients with SLE and 36 healthy controls were tested with RT-PCR assay.The activation of Pyk2 was inhibited using specific inhibitor Pyk2 (TyrA9).Semi-quantitative PCR methodwas used to detect the Blys expression of PBMCs.One-way ANOVA and Pearson's correlation analysis were used for statistical analysis.Results The Pyk2 expression level (28.31 ±0.91) of SLE patients was significantly higher than that in healthy controls (33.69±0.04),the difference was statistically significant (P＜0.05).The activation of Pyk2 was stimulated and the expression levels of Blys in the PBMCs of patients with SLE was elevated.By inhibiting the activation of Pyk2,the BLyS expression levels decreased significantly.Conclusion Pyk2 may be involved in the abnormal activation of lymphocytes which lead to the pathogenesis of SLE.Pyk2 expression is associated with SLE disease activity,disease aggravation,and the Pyk2 expression levels is also increased significantly.In addition,the expression level of Pyk2 is higher in patients with renal involvement than those patients with other organ involvement.

Effect of intravenous immunoglobulin on IFN-? and IL-4 production of cord blood lymphocytes in neonates / 中华围产医学杂志

Objective To study the effects of intravenous immunoglobulin (IVIG) on neonatal lymphocyte immune function. Methods Cord blood mononuclear cells (CBMCs) and CD3+ T lymphocytes were isolated from 8 neonates and were cultured with IVIG and/or/without phytohemagglutinin (PHA)based on which divided into five groups, i. e. (l)control group, (2)PHA activation group, (3) IVIG pre-inhibition group, (4) PHA pre-activation group and (5) PHA+IVIG group. The production of IFN-? and IL-4 of CBMCs and cord blood CD3+ T lymphocytes was measured with ELISA and the expression of IL-2 and IL-4 mRNA was measured with RT-PCR. The results were compared with peripheral blood mononuclear cells(PBMCs) of 8 adults. Results The production of IFN-y by CBMCs and cord blood CD3+ T lymphocytes induced by PHA decreased after IVIG was given, while more remarkable decrease in the CBMCs was shown without any association with IVIG was given or not before or after PHA was used [Group 2; (313. 34?108. 00)pg/ml, Group 3: (17. 68?17. 98) pg/ml, group 4 : (170. 72?38. 25) pg/ml, group 5: (11. 10?8. 92)pg/ml]. For the CD3+ T lymphocytes, the decrease of IFN-? production was only observed in group 3, 4 and group 5 [(35. 30 ?12. 21)pg/ml, (8. 61?6. 21) pg/ml and (8. 54?1. 57)pg/ml]. The degree of decrease of IFN-? production by CBMCs was much lower [group 2: (1121. 11 ? 344. 58)pg/ml, group 3: (29. 08 ? 11. 20)pg/ml, group 4: (339. 63?47. 43) pg/ml, group 5: (26.40?21. 97)pg/ml]. The secretion for IL-4 did not changed when stimulated by PHA alone, but IL-2 and IL-4 mRNAs expression can be detected in CBMCs after repeated stimulation by PMA, PHA and rIL-2 which decreased after IVIG was given. Conclusions IVIG can suppress the production of IFN-? in cord blood T lymphocyte directly or mediated by other immune cells or molecules. IVIG can also decreased the expression of IL-2 mRNA and IL-4 mRNA in CBMCs. The effect of IVIG on the proliferation of cord blood lymphocytes and production of immunoglobulin in B lymphocytes might be associated with these inhibition.